Pathology in Practice

Sarah D. Cramer Departments of Veterinary Pathobiology, Center for Veterinary Health Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078.

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Melanie A. Breshears Departments of Veterinary Pathobiology, Center for Veterinary Health Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078.

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Heath J. Qualls Veterinary Clinical Sciences, Center for Veterinary Health Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078.

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History

A 23-year-old Paint gelding was brought to the Oklahoma State University Boren Veterinary Medical Teaching Hospital to be euthanatized because of a progressively enlarging mass on the glans penis and enlargement of the prepuce.

Clinical and Gross Findings

Because euthanasia was to be performed, a limited physical examination of the horse was undertaken. The horse was mildly lethargic and had a body condition score of 3/9. Severe edema of the prepuce and inguinal areas made examination difficult. Maggots were present at the preputial opening, and a foul smell emanated from the tissue. The horse walked with a stilted gait in the hind limbs, presumably because of regional edema and pain. After the examination, euthanasia was performed via IV administration of pentobarbital solution. The carcass of the horse was submitted to the Oklahoma Animal Disease and Diagnostic Laboratory for necropsy.

At necropsy, the prepuce was severely edematous and the penis was difficult to extend from the sheath (phimosis). The normal anatomic features of the glans penis were severely disrupted by a large, multinodular, exophytic mass that was firm, yellow to tan, and mottled with multiple cystic cavities containing caseous debris surrounded by dense fibrous connective tissue. The mass encroached upon the urethra, distorting and narrowing the distal third of the lumen. Dozens of maggots infiltrated the necrotic tissue of the glans (Figure 1). In addition, superficial inguinal, deep inguinal, and sublumbar lymph nodes were markedly enlarged. On cut surface, the nodes were yellow to tan and mottled with small, cystic cavities that contained caseous debris. Many 1- to 6-cm-diameter, firm, red-to-white mottled nodules were scattered randomly throughout all lung lobes. Mediastinal lymph nodes were enlarged and partially effaced and replaced by yellow, caseous material. On examination of the heart, a 1-cm-diameter, firm, yellow-to-tan nodule was detected within the myocardium of the interventricular septum.

Figure 1—
Figure 1—

Photographs of the glans penis and prepuce (A) and lungs (B) of a horse that was euthanatized because of a progressively enlarging mass on the glans penis and enlargement of the prepuce. The normal glans architecture is partially effaced by an exophytic, multinodular mass, and the prepuce is markedly edematous. The lungs have numerous variably sized nodules scattered throughout the parenchyma.

Citation: Journal of the American Veterinary Medical Association 238, 5; 10.2460/javma.238.5.581

Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →

Histopathologic Findings

Histologic examination of sections of the skin of the glans penis revealed a highly invasive neoplasm that was composed of islands of squamous to basaloid epithelium surrounded by abundant fibrous connective tissue. Cells were often connected via prominent intercellular bridges. Individual cells were round to polygonal with variable amounts of eosinophilic cytoplasm that was occasionally keratinized. The number of mitoses varied between individual fields of view, and there was a total of 24 mitotic figures in 10 hpf (magnification, 400×). Areas of coagulative necrosis were scattered throughout the neoplastic tissue, and some areas were infiltrated by lymphocytes and plasma cells. The pelvic lymph nodes, tracheobronchial lymph nodes, and nodules in the lungs and heart were composed of similar neoplastic epithelial cells (Figure 2).

Figure 2—
Figure 2—

Photomicrographs of a section of the cardiac interventricular septum of the horse in Figure 1. Notice that nests of neoplastic epithelial cells have invaded the myocardium. At higher magnification (inset), it is evident that the metastatic cells have prominent intercellular bridges (arrow) and occasional cytoplasmic keratinization (arrowhead), which are characteristic of squamous cell carcinoma. H&E stain; bar in main image and inset panel = 100 and 10 μm, respectively.

Citation: Journal of the American Veterinary Medical Association 238, 5; 10.2460/javma.238.5.581

Morphologic Diagnosis

Squamous cell carcinoma of the penis with multifocal metastasis to the regional lymph nodes, lungs, and heart.

Comments

Squamous cell carcinoma is the most common neoplasm of the penis and prepuce in horses; it comprises 67.5%1 to 85.4% (excluding sarcoids)2 of genital neoplasms in male horses. Commonly affected sites include the glans penis (17%) and the prepuce (27.6%).3 The urethra is often secondarily involved (27.6%).2 Older horses are typically affected; mean age of affected horses ranges from 174 to 19.8 years.1

In addition to squamous cell carcinoma, differential diagnoses for the lesions in the horse of this report included less commonly reported neoplasms of the equine penis and prepuce such as squamous papilloma,2 fibrosarcoma, adenocarcinoma, neurofibroma, basal cell carcinoma, and melanoma.1 Nonneoplastic differential diagnoses included epithelial hyperplasia; cutaneous infection with Habronema spp,2 Halicephalobus spp,5 or Draschia megastoma; or coital exanthema (infection with equine herpesvirus 3).6 For antemortem diagnosis, results of microscopic examination of cutaneous biopsy specimens or possibly aspirate samples of the lesions are useful.

In horses with penile squamous cell carcinoma, common clinical signs include preputial discharge, preputial bleeding, and preputial masses. As illustrated by the horse of this report, many affected horses are not examined by a veterinarian until the neoplasm has extensively invaded surrounding tissues.1,2 Some horses may have difficulty urinating, phimosis, and preputial edema; less specific signs include lameness and a lack of stamina.1

Metastasis of penile squamous cell carcinoma to regional lymph nodes is not uncommon, and lymph node metastasis is detected in 12% of cases.2 However, not all enlarged lymph nodes contain neoplastic infiltrates. In a study1 of 114 horses with penile or preputial tumors, the causes of enlargement of 19 of 28 (68%) lymph nodes were regional inflammation and secondary lymphoid hyperplasia, rather than metastasis.

Distant metastasis to other organs or tissues is less common, and the most frequently reported sites include the lungs7,8 and liver.9 Other reported sites of metastasis include the abdomen10 and the thoracic vertebral column (without evidence of regional lymph node metastasis).11 Myocardial metastasis, as detected in the horse of this report, is exceedingly rare. To our knowledge, the only other published report7 describes myocardial metastasis (ie, nodules in the myocardium that were classified as undifferentiated carcinoma) that was presumed to develop from penile squamous cell carcinoma in a horse. In the horse of this report, metastatic cells had prominent intercellular bridges but only occasional cytoplasmic keratinization, consistent with an immature phenotype. Because most cells were immature, the neoplasm was classified as poorly differentiated. In a study1 of penile squamous cell carcinoma in horses, neoplasms were graded according to their degree of differentiation. Similar to findings in the horse of this report, results of that study1 indicated that the rate of metastasis for poorly differentiated neoplasms was higher than that for well-differentiated neoplasms. In addition to the poorly differentiated nature of the neoplasm in the horse of this report, the high mitotic rate and multifocal areas of necrosis were suggestive of increased malignant potential.

The specific cause of the development of genital squamous cell carcinoma is unclear. In horses, it has been hypothesized that smegma may be carcinogenic,12 although a similar theory has generated controversy in the human medical literature.13,14 Furthermore, research has failed to determine a viral etiology; papilloma virus particles are present in squamous papillomas but not in squamous cell carcinomas.15 Ultraviolet irradiation via sun exposure has been suggested as a possible inciting cause because genital squamous cell carcinomas often develop on lightly pigmented areas.16 However, the role of UV irradiation in development of penile squamous cell carcinoma is unclear, as results of 1 study2 suggested that light coat color does not predispose horses to developing penile squamous cell carcinoma.

Treatment of penile or preputial squamous cell carcinoma depends on the extent and location of the lesion. Small, superficial masses may be treated by removal of the mass and surrounding tissue. However, larger, more invasive masses may require extensive surgical procedures to remove the affected tissue. Surgical methods include cryosurgery, posthectomy, phallectomy, and en bloc resection.6,17 Topical chemotherapy with 5-fluorouracil is also effective.18 In a retrospective study17 of 77 male horses with squamous cell carcinoma of the external genitalia, surgical treatment was effective in 55.7% of cases; moreover, horses treated with partial phallectomy were more likely to have recurrent neoplasia, compared with horses treated with en bloc resection. In addition, a recently developed technique for penile amputation and sheath ablation with pexy of the urethra to the abdominal wall has been reported to reduce the postoperative complications that are common with en bloc resection and phallectomy.19

References

  • 1.

    van den Top JG, de Heer N, Klein WR, et al. Penile and preputial tumours in the horse: a retrospective study of 114 affected horses. Equine Vet J 2008; 40:528532.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Howarth S, Lucke VM, Pearson H. Squamous cell carcinoma of the equine external genitalia: a review and assessment of penile amputation and urethrostomy as a surgical treatment. Equine Vet J 1991; 23:5358.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Strafuss AC. Squamous cell carcinoma in horses. J Am Vet Med Assoc 1976; 168:6162.

  • 4.

    Valentine BA. Survey of equine cutaneous neoplasia in the Pacific Northwest. J Vet Diagn Invest 2006; 18:123126.

  • 5.

    Muller S, Grzybowski M, Sager H, et al. A nodular granulomatous posthitis caused by Halicephalobus sp. in a horse. Vet Dermatol 2008; 19:4448.

    • Search Google Scholar
    • Export Citation
  • 6.

    Varner DD, Schumacher J. Diseases of the penis. In: Colahan PT, Mayhew IG, Merritt AM, et al, eds. Equine medicine and surgery. 5th ed. St Louis: Mosby, 1999;10611077.

    • Search Google Scholar
    • Export Citation
  • 7.

    Markel MD, Wheat JD, Jones K. Genital neoplasms treated by en bloc resection and penile retroversion in horses: 10 cases (1977–1986). J Am Vet Med Assoc 1988; 192:396400.

    • Search Google Scholar
    • Export Citation
  • 8.

    Perez J, Mozos E, Martin MP, et al. Immunohistochemical study of the inflammatory infiltrate associated with equine squamous cell carcinoma. J Comp Pathol 1999; 121:385397.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Foster RS, Ladds PW. Male genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's pathology of domestic animals. 5th ed. Edinburgh: Saunders, 2007;618.

    • Search Google Scholar
    • Export Citation
  • 10.

    Mair TS, Walmsley JP, Phillips TJ. Surgical treatment of 45 horses affected by squamous cell carcinoma of the penis and prepuce. Equine Vet J 2000; 32:406410.

    • Search Google Scholar
    • Export Citation
  • 11.

    Patterson LJ, May SA, Baker JR. Skeletal metastasis of a penile squamous cell carcinoma. Vet Rec 1990; 126:579580.

  • 12.

    Plaut A, Kohn-Speyer AC. The carcinogenic action of smegma. Science 1947; 105:391392.

  • 13.

    Van Howe RS, Hodges FM. The carcinogenicity of smegma: debunking a myth. J Eur Acad Dermatol Venereol 2006; 20:10461054.

  • 14.

    Waskett JH, Morris BJ. Re: ‘RS Van Howe, FM Hodges. The carcinogenicity of smegma: debunking a myth.’ An example of myth and mythchief making? J Eur Acad Dermatol Venereol 2008; 22:131132.

    • Search Google Scholar
    • Export Citation
  • 15.

    Junge RE, Sundberg JP, Lancaster WD. Papillomas and squamous cell carcinomas of horses. J Am Vet Med Assoc 1984; 185:656659.

  • 16.

    MacLachlan NJ, Kennedy PC. Tumors of the genital systems. In: Meuten DJ, ed. Tumors in domestic animals. 4th ed. Ames, Iowa: Iowa State Press, 2002;572.

    • Search Google Scholar
    • Export Citation
  • 17.

    van den Top JG, de Heer N, Klein WR, et al. Penile and preputial squamous cell carcinoma in the horse: a retrospective study of treatment of 77 affected horses. Equine Vet J 2008; 40:533537.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Fortier LA, Mac Harg MA. Topical use of 5-fluorouracil for treatment of squamous cell carcinoma of the external genitalia of horses: 11 cases (1988–1992). J Am Vet Med Assoc 1994; 205:11831185.

    • Search Google Scholar
    • Export Citation
  • 19.

    Doles J, Williams JW, Yarbrough TB. Penile amputation and sheath ablation in the horse. Vet Surg 2001; 30:327331.

  • Figure 1—

    Photographs of the glans penis and prepuce (A) and lungs (B) of a horse that was euthanatized because of a progressively enlarging mass on the glans penis and enlargement of the prepuce. The normal glans architecture is partially effaced by an exophytic, multinodular mass, and the prepuce is markedly edematous. The lungs have numerous variably sized nodules scattered throughout the parenchyma.

  • Figure 2—

    Photomicrographs of a section of the cardiac interventricular septum of the horse in Figure 1. Notice that nests of neoplastic epithelial cells have invaded the myocardium. At higher magnification (inset), it is evident that the metastatic cells have prominent intercellular bridges (arrow) and occasional cytoplasmic keratinization (arrowhead), which are characteristic of squamous cell carcinoma. H&E stain; bar in main image and inset panel = 100 and 10 μm, respectively.

  • 1.

    van den Top JG, de Heer N, Klein WR, et al. Penile and preputial tumours in the horse: a retrospective study of 114 affected horses. Equine Vet J 2008; 40:528532.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Howarth S, Lucke VM, Pearson H. Squamous cell carcinoma of the equine external genitalia: a review and assessment of penile amputation and urethrostomy as a surgical treatment. Equine Vet J 1991; 23:5358.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Strafuss AC. Squamous cell carcinoma in horses. J Am Vet Med Assoc 1976; 168:6162.

  • 4.

    Valentine BA. Survey of equine cutaneous neoplasia in the Pacific Northwest. J Vet Diagn Invest 2006; 18:123126.

  • 5.

    Muller S, Grzybowski M, Sager H, et al. A nodular granulomatous posthitis caused by Halicephalobus sp. in a horse. Vet Dermatol 2008; 19:4448.

    • Search Google Scholar
    • Export Citation
  • 6.

    Varner DD, Schumacher J. Diseases of the penis. In: Colahan PT, Mayhew IG, Merritt AM, et al, eds. Equine medicine and surgery. 5th ed. St Louis: Mosby, 1999;10611077.

    • Search Google Scholar
    • Export Citation
  • 7.

    Markel MD, Wheat JD, Jones K. Genital neoplasms treated by en bloc resection and penile retroversion in horses: 10 cases (1977–1986). J Am Vet Med Assoc 1988; 192:396400.

    • Search Google Scholar
    • Export Citation
  • 8.

    Perez J, Mozos E, Martin MP, et al. Immunohistochemical study of the inflammatory infiltrate associated with equine squamous cell carcinoma. J Comp Pathol 1999; 121:385397.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Foster RS, Ladds PW. Male genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's pathology of domestic animals. 5th ed. Edinburgh: Saunders, 2007;618.

    • Search Google Scholar
    • Export Citation
  • 10.

    Mair TS, Walmsley JP, Phillips TJ. Surgical treatment of 45 horses affected by squamous cell carcinoma of the penis and prepuce. Equine Vet J 2000; 32:406410.

    • Search Google Scholar
    • Export Citation
  • 11.

    Patterson LJ, May SA, Baker JR. Skeletal metastasis of a penile squamous cell carcinoma. Vet Rec 1990; 126:579580.

  • 12.

    Plaut A, Kohn-Speyer AC. The carcinogenic action of smegma. Science 1947; 105:391392.

  • 13.

    Van Howe RS, Hodges FM. The carcinogenicity of smegma: debunking a myth. J Eur Acad Dermatol Venereol 2006; 20:10461054.

  • 14.

    Waskett JH, Morris BJ. Re: ‘RS Van Howe, FM Hodges. The carcinogenicity of smegma: debunking a myth.’ An example of myth and mythchief making? J Eur Acad Dermatol Venereol 2008; 22:131132.

    • Search Google Scholar
    • Export Citation
  • 15.

    Junge RE, Sundberg JP, Lancaster WD. Papillomas and squamous cell carcinomas of horses. J Am Vet Med Assoc 1984; 185:656659.

  • 16.

    MacLachlan NJ, Kennedy PC. Tumors of the genital systems. In: Meuten DJ, ed. Tumors in domestic animals. 4th ed. Ames, Iowa: Iowa State Press, 2002;572.

    • Search Google Scholar
    • Export Citation
  • 17.

    van den Top JG, de Heer N, Klein WR, et al. Penile and preputial squamous cell carcinoma in the horse: a retrospective study of treatment of 77 affected horses. Equine Vet J 2008; 40:533537.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Fortier LA, Mac Harg MA. Topical use of 5-fluorouracil for treatment of squamous cell carcinoma of the external genitalia of horses: 11 cases (1988–1992). J Am Vet Med Assoc 1994; 205:11831185.

    • Search Google Scholar
    • Export Citation
  • 19.

    Doles J, Williams JW, Yarbrough TB. Penile amputation and sheath ablation in the horse. Vet Surg 2001; 30:327331.

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